Special Issue "Therapeutic Targets and Personalized Medicine in Cardiac Disease"

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: 30 November 2022 | Viewed by 8476

Special Issue Editors

Dr. Elizabeth Vafiadaki
E-Mail Website
Guest Editor
Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou St, 115-27 Athens, Greece
Interests: cardiac cell biology; calcium homeostasis; cardiovascular physiology; cardiac disease; personalized medicine
Special Issues, Collections and Topics in MDPI journals
Dr. Despina Sanoudou
E-Mail Website
Guest Editor
Clinical Genomics and Pharmacogenomics Unit, 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Building 15, Mikras Asias 75, 115-27 Athens, Greece
Interests: pharmacogenomics; molecular cardiology; precision medicine
Special Issues, Collections and Topics in MDPI journals
Dr. Irene Turnbull
E-Mail Website
Guest Editor
Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl, Box 1030, New York, NY 10029, USA
Interests: cardiac tissue engineering; adult stem cells; human induced pluripotent stem cells; cardiac contractility; cardiac disease models

Special Issue Information

Dear Colleagues,

Cardiovascular disease has been the subject of extensive research and notable advancements over decades. However, it remains the leading cause of death, with millions affected worldwide. The available therapeutic options leave a lot to be desired in many cases, while they remain non-existent in others. Importantly, there are many cases where prognosis is challenging and response to treatment highly variable. Even when the cause has a genetic basis, different mutations within the same gene can result in different pathophysiology, while the same gene mutation can lead to variable phenotypes. The remarkable technological advancements and scientific breakthroughs over recent years are unveiling a horizon of new possibilities. Notable examples range from multi-omics analyses as fine as single-cell level and sophisticated artificial intelligence tools, to highly targeted gene therapy, RNAi, and CRISPR approaches.

This Special Issue focuses on cutting-edge developments in the discovery of novel CVD targets and the development of personalized therapeutic approaches. We invite the submission of original research and review articles on the latest scientific advances toward understanding and combating CVD in the Precision Medicine era. 

Dr. Elizabeth Vafiadaki
Dr. Despina Sanoudou
Dr. Irene C. Turnbull
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cardiovascular disease 
  • Personalized medicine 
  • Precision medicine 
  • Pharmacogenomics 
  • Molecular Cardiology 
  • Genetic mutation 
  • Disease pathogenesis 
  • Translational research 
  • Targeted therapies

Published Papers (6 papers)

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Research

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Article
Precision Medicine in Aortic Anastomosis: A Numerical and Experimental Study of a Novel Double-Sided Needle
J. Pers. Med. 2021, 11(12), 1385; https://doi.org/10.3390/jpm11121385 - 20 Dec 2021
Viewed by 883
Abstract
Background: Hand-sewn anastomosis is a crucial part of aortic reconstruction surgery and significantly affects its outcome. The present study presents a novel, bidirectional surgical needle aimed to improve aortic anastomosis in terms of speed and ease of use. Our objective was to assess [...] Read more.
Background: Hand-sewn anastomosis is a crucial part of aortic reconstruction surgery and significantly affects its outcome. The present study presents a novel, bidirectional surgical needle aimed to improve aortic anastomosis in terms of speed and ease of use. Our objective was to assess the efficacy of the new design in comparison with the conventional needle. Methods: A series of simulations were conducted with COMSOL software in order to perform a fatigue comparative analysis between the new and the conventional needle design. Ease of penetration into a piece of polydimethylsiloxane was evaluated. Lastly, the prototype was tested under in-vitro conditions in comparison with the conventional needle. Results: Based on fatigue analysis, the new needle design improves durability, provided the two tips are equally used. The polytetrafluoroethylene coating improves penetration into the tissue by 7% to 17%, while electropolishing improves penetration up to 19%. When using the novel needle design, the average anastomotic task completion time was significantly reduced by 22% and the overall distance of hand movements was significantly reduced by 20%. Conclusions: The proposed design exhibited a shorter anastomotic time and seems promising in relation to ease of use and simplicity of the anastomotic technique it introduces. Full article
(This article belongs to the Special Issue Therapeutic Targets and Personalized Medicine in Cardiac Disease)
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Article
Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias
J. Pers. Med. 2021, 11(6), 502; https://doi.org/10.3390/jpm11060502 - 03 Jun 2021
Cited by 3 | Viewed by 1817
Abstract
The inherited mutation (R14del) in the calcium regulatory protein phospholamban (PLN) is linked to malignant ventricular arrhythmia with poor prognosis starting at adolescence. However, the underlying early mechanisms that may serve as prognostic factors remain elusive. This study generated humanized mice in which [...] Read more.
The inherited mutation (R14del) in the calcium regulatory protein phospholamban (PLN) is linked to malignant ventricular arrhythmia with poor prognosis starting at adolescence. However, the underlying early mechanisms that may serve as prognostic factors remain elusive. This study generated humanized mice in which the endogenous gene was replaced with either human wild type or R14del-PLN and addressed the early molecular and cellular pathogenic mechanisms. R14del-PLN mice exhibited stress-induced impairment of atrioventricular conduction, and prolongation of both ventricular activation and repolarization times in association with ventricular tachyarrhythmia, originating from the right ventricle (RV). Most of these distinct electrocardiographic features were remarkably similar to those in R14del-PLN patients. Studies in isolated cardiomyocytes revealed RV-specific calcium defects, including prolonged action potential duration, depressed calcium kinetics and contractile parameters, and elevated diastolic Ca-levels. Ca-sparks were also higher although SR Ca-load was reduced. Accordingly, stress conditions induced after contractions, and inclusion of the CaMKII inhibitor KN93 reversed this proarrhythmic parameter. Compensatory responses included altered expression of key genes associated with Ca-cycling. These data suggest that R14del-PLN cardiomyopathy originates with RV-specific impairment of Ca-cycling and point to the urgent need to improve risk stratification in asymptomatic carriers to prevent fatal arrhythmias and delay cardiomyopathy onset. Full article
(This article belongs to the Special Issue Therapeutic Targets and Personalized Medicine in Cardiac Disease)
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Article
Creating a ‘Molecular Band-Aid’; Blocking an Exposed Protease Target Site in Desmoplakin
J. Pers. Med. 2021, 11(5), 401; https://doi.org/10.3390/jpm11050401 - 12 May 2021
Cited by 1 | Viewed by 794
Abstract
Desmoplakin (DSP) is a large (~260 kDa) protein found in the desmosome, a subcellular complex that links the cytoskeleton of one cell to its neighbor. A mutation ‘hot-spot’ within the NH2-terminal third of the DSP protein (specifically, residues 299–515) is associated [...] Read more.
Desmoplakin (DSP) is a large (~260 kDa) protein found in the desmosome, a subcellular complex that links the cytoskeleton of one cell to its neighbor. A mutation ‘hot-spot’ within the NH2-terminal third of the DSP protein (specifically, residues 299–515) is associated with both cardiomyopathies and skin defects. In select DSP variants, disease is linked specifically to the uncovering of a previously-occluded calpain target site (residues 447–451). Here, we partially stabilize these calpain-sensitive DSP clinical variants through the addition of a secondary single point mutation—tyrosine for leucine at amino acid position 518 (L518Y). Molecular dynamic (MD) simulations and enzymatic assays reveal that this stabilizing mutation partially blocks access to the calpain target site, resulting in restored DSP protein levels. This ‘molecular band-aid’ provides a novel way to maintain DSP protein levels, which may lead to new strategies for treating this subset of DSP-related disorders. Full article
(This article belongs to the Special Issue Therapeutic Targets and Personalized Medicine in Cardiac Disease)
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Review

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Review
The Challenge and Importance of Integrating Drug–Nutrient–Genome Interactions in Personalized Cardiovascular Healthcare
J. Pers. Med. 2022, 12(4), 513; https://doi.org/10.3390/jpm12040513 - 22 Mar 2022
Viewed by 930
Abstract
Despite the rich armamentarium of available drugs against different forms of cardiovascular disease (CVD), major challenges persist in their safe and effective use. These include high rates of adverse drug reactions, increased heterogeneity in patient responses, suboptimal drug efficacy, and in some cases [...] Read more.
Despite the rich armamentarium of available drugs against different forms of cardiovascular disease (CVD), major challenges persist in their safe and effective use. These include high rates of adverse drug reactions, increased heterogeneity in patient responses, suboptimal drug efficacy, and in some cases limited compliance. Dietary elements (including food, beverages, and supplements) can modulate drug absorption, distribution, metabolism, excretion, and action, with significant implications for drug efficacy and safety. Genetic variation can further modulate the response to diet, to a drug, and to the interaction of the two. These interactions represent a largely unexplored territory that holds considerable promise in the field of personalized medicine in CVD. Herein, we highlight examples of clinically relevant drug–nutrient–genome interactions, map the challenges faced to date, and discuss their future perspectives in personalized cardiovascular healthcare in light of the rapid technological advances. Full article
(This article belongs to the Special Issue Therapeutic Targets and Personalized Medicine in Cardiac Disease)
Review
The Potential of Hsp90 in Targeting Pathological Pathways in Cardiac Diseases
J. Pers. Med. 2021, 11(12), 1373; https://doi.org/10.3390/jpm11121373 - 16 Dec 2021
Viewed by 1715
Abstract
Heat shock protein 90 (Hsp90) is a molecular chaperone that interacts with up to 10% of the proteome. The extensive involvement in protein folding and regulation of protein stability within cells makes Hsp90 an attractive therapeutic target to correct multiple dysfunctions. Many of [...] Read more.
Heat shock protein 90 (Hsp90) is a molecular chaperone that interacts with up to 10% of the proteome. The extensive involvement in protein folding and regulation of protein stability within cells makes Hsp90 an attractive therapeutic target to correct multiple dysfunctions. Many of the clients of Hsp90 are found in pathways known to be pathogenic in the heart, ranging from transforming growth factor β (TGF-β) and mitogen activated kinase (MAPK) signaling to tumor necrosis factor α (TNFα), Gs and Gq g-protein coupled receptor (GPCR) and calcium (Ca2+) signaling. These pathways can therefore be targeted through modulation of Hsp90 activity. The activity of Hsp90 can be targeted through small-molecule inhibition. Small-molecule inhibitors of Hsp90 have been found to be cardiotoxic in some cases however. In this regard, specific targeting of Hsp90 by modulation of post-translational modifications (PTMs) emerges as an attractive strategy. In this review, we aim to address how Hsp90 functions, where Hsp90 interacts within pathological pathways, and current knowledge of small molecules and PTMs known to modulate Hsp90 activity and their potential as therapeutics in cardiac diseases. Full article
(This article belongs to the Special Issue Therapeutic Targets and Personalized Medicine in Cardiac Disease)
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Review
The Potential of Gamma Secretase as a Therapeutic Target for Cardiac Diseases
J. Pers. Med. 2021, 11(12), 1294; https://doi.org/10.3390/jpm11121294 - 04 Dec 2021
Viewed by 1243
Abstract
Heart diseases are some of the most common and pressing threats to human health worldwide. The American Heart Association and the National Institute of Health jointly work to annually update data on cardiac diseases. In 2018, 126.9 million Americans were reported as having [...] Read more.
Heart diseases are some of the most common and pressing threats to human health worldwide. The American Heart Association and the National Institute of Health jointly work to annually update data on cardiac diseases. In 2018, 126.9 million Americans were reported as having some form of cardiac disorder, with an estimated direct and indirect total cost of USD 363.4 billion. This necessitates developing therapeutic interventions for heart diseases to improve human life expectancy and economic relief. In this review, we look into gamma-secretase as a potential therapeutic target for cardiac diseases. Gamma-secretase, an aspartyl protease enzyme, is responsible for the cleavage and activation of a number of substrates that are relevant to normal cardiac development and function as found in mutation studies. Some of these substrates are involved in downstream signaling processes and crosstalk with pathways relevant to heart diseases. Most of the substrates and signaling events we explored were found to be potentially beneficial to maintain cardiac function in diseased conditions. This review presents an updated overview of the current knowledge on gamma-secretase processing of cardiac-relevant substrates and seeks to understand if the modulation of gamma-secretase activity would be beneficial to combat cardiac diseases. Full article
(This article belongs to the Special Issue Therapeutic Targets and Personalized Medicine in Cardiac Disease)
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